Phased Exploratory Clinical Studies of Harpagophytum procumbens' Impact upon the Biological Signature of inflammatory Osteoarthritis.

Harpagophytum procumbens 对炎症性骨关节炎生物学特征影响的分阶段探索性临床研究。

• 批准号: 9771124
• 负责人: William Robert Folk
• 金额: $ 29.51万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9771124
• 关键词: Phased; Exploratory; Clinical; Studies; Harpagophytum

 DESCRIPTION (provided by applicant): Musculoskeletal conditions represent a major source of pain, loss of function, and health care expenditure that costs Americans many billions, yearly. People with conditions causing chronic pain turn to integrative health practices to supplement other conventional medical treatment, or when their pain is resistant to or in an effort to avoid side effects of medications. However, scientific evidence of safety, efficacy and mechanisms of such practices are limited. European clinical research has provided evidence for safety and efficacy of the botanical Harpagophytum procumbens (H. procumbens or Devil's Claw) for many patients suffering from arthritis and chronic low back pain. The variability in the natural products, however, and lack of a well-defined biological signature necessitate additional exploratory studies with well-characterized products, so that subsequent clinical studies of appropriate methodological rigor can be conducted. The proposed project will use a well characterized product to assess a biological signature for a hypothesized mechanism of action. The R21 phase of the proposed project will address the following objectives: (1) further define the bioavailability and short term pharmacokinetics of the principal secondary metabolites of a well-characterized aqueous-ethanolic extract of H. procumbens in non-enteric and enteric formulations; (2) define the biological signature and hypothetical mechanism of action of the H. procumbens extract in patients with early stage inflammatory knee osteoarthritis over four week dosing; and, (3) develop protocol, data and safety monitoring plan and manual of operations/procedures and obtain all necessary regulatory approvals for the R33 phase. Following successful completion of the R21 phase, the following objectives will be addressed during the R33 phase: (1) confirm and extend assessment of the impact of the H. procumbens extract upon the biological signature of the above referenced systemic inflammatory biomarkers and biomarkers in synovial fluid of patients consuming either of two doses over twelve weeks; and, (2) evaluate the relationship between changes in systemic and local joint biomarker levels and clinical outcomes (pain, stiffness, functional difficulty). Completion of this study will ensure that future clinical trials can be conducted with the methodological rigor and outcome measures needed to appropriately evaluate the effectiveness of H. procumbens products.

 描述（由申请人提供）：肌肉骨骼疾病是疼痛、功能丧失和医疗保健支出的主要来源，每年使美国人花费数十亿美元。患有导致慢性疼痛的疾病的人会转向综合健康实践来补充其他传统的医疗方法，或者当他们的疼痛对药物有抵抗力或试图避免药物的副作用时。然而，此类做法的安全性、有效性和机制的科学证据有限。欧洲临床研究已为植物性 Harpagophytum procumbens（H. procumbens 或 Devil's Claw）对许多患有关节炎和慢性腰痛的患者的安全性和有效性提供了证据。然而，天然产物的变异性以及缺乏明确的生物学特征需要对特征明确的产品进行额外的探索性研究，以便能够进行适当方法学严格性的后续临床研究。拟议的项目将使用一种特征良好的产品来评估假设的作用机制的生物特征。拟议项目的 R21 阶段将实现以下目标：（1）进一步确定非肠溶和肠溶制剂中经过充分表征的 H. procumbens 水乙醇提取物的主要次生代谢物的生物利用度和短期药代动力学； (2) 确定 H. procumbens 提取物在服药 4 周后对早期炎症性膝骨关节炎患者的生物学特征和假设作用机制； (3) 制定方案、数据和安全监测计划以及操作/程序手册，并获得 R33 阶段所有必要的监管批准。成功完成 R21 阶段后，将在 R33 阶段实现以下目标：(1) 确认并扩展评估 H. procumbens 提取物对上述提及的全身炎症生物标志物和在 12 周内服用两剂中任一剂量的患者滑液中生物标志物的生物特征的影响； (2) 评估全身和局部关节生物标志物水平的变化与临床结果（疼痛、僵硬、功能困难）之间的关系。这项研究的完成将确保未来的临床试验能够以适当评估 H. procumbens 产品有效性所需的方法学严谨性和结果测量进行。

项目成果

Toxicology studies of aqueous-alcohol extracts of Harpagophytum procumbens subsp. procumbens (Burch.) DC.Ex Meisn. (Pedaliaceae) in female and male rats.

Harpagophytum procumbens subsp. 水醇提取物的毒理学研究。

• DOI: 10.1186/s12906-019-2789-9
• 发表时间: 2020
• 期刊: BMC complementary medicine and therapies
• 影响因子: 3.9
• 作者: Joshi,Kirtan;Parrish,Alan;Grunz-Borgmann,ElizabethA;Gerkovich,Mary;Folk,WilliamR
• 通讯作者: Folk,WilliamR